Belatacept Injection for Kidney Transplant

Overseen By Piotr Witkowski, M.D. Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Chicago

Must be taking: Proteasome inhibitors

Must not be taking: Investigational drugs, Live vaccines

Disqualifiers: Neuropathy, Heart disease, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

5 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if using belatacept (an injection) with a proteasome inhibitor can help more people find suitable kidney donors. It targets individuals who are highly HLA sensitized, meaning their bodies are likely to reject a kidney, making it difficult to find a match. Participants should currently be waiting for a kidney transplant at the University of Chicago and have been living with this challenge. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking investigational drugs, you must stop them at least 14 days before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that belatacept has been tested for safety in kidney transplant patients. In one study, patients who switched to belatacept had better kidney function after one year compared to those on other treatments. Another study found that after five years, 76% of patients on belatacept were still doing well. However, a virus infection can pose a risk of kidney problems, possibly requiring a change in treatment.

In this trial, belatacept is used with a proteasome inhibitor. Although specific data for this combination is not available, studies on belatacept alone indicate it can be well-tolerated by many patients. The trial is in the early stages, so researchers are closely monitoring safety. Participants will have regular check-ups for any side effects or health issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard immunosuppressive therapies used for kidney transplants, like tacrolimus or cyclosporine, belatacept offers a novel approach by selectively blocking the co-stimulation of T-cells, which are crucial in the immune response that can lead to organ rejection. This targeted action may reduce the risk of chronic kidney damage and other side effects associated with long-term use of traditional immunosuppressants. Researchers are excited about belatacept because it has the potential to improve transplant outcomes by specifically decreasing the calculated Panel of Reactive Antibodies (cPRA), which could expand the pool of suitable donor kidneys for highly sensitized patients.

What evidence suggests that belatacept might be an effective treatment for kidney transplant candidates?

Research has shown that belatacept can improve outcomes for kidney transplant patients. Studies have found that belatacept significantly reduces the risk of death and loss of the transplanted kidney. For instance, one study discovered that after 7 years, a more intensive belatacept treatment reduced the risk of death by 38%. Additionally, patients using belatacept often experience better kidney function over time. In this trial, participants will receive belatacept and a proteasome inhibitor, which may help highly sensitized patients by increasing the chances of finding a suitable donor match based on a negative crossmatch. ^{3 4 5 6 7}

Who Is on the Research Team?

Piotr Witkowski, MD PhD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for highly sensitized kidney transplant candidates who are EBV IgG positive, have no active infections or allergies to the drugs being tested, and are not pregnant. They must be vaccinated against COVID-19 and hepatitis B, listed for a transplant at University of Chicago, and agree to use two contraception methods post-treatment.

Inclusion Criteria

You are currently on the waiting list for a kidney transplant at the University of Chicago Transplant Institute.

I have been fully vaccinated against COVID-19 for at least 2 weeks.

I have antibodies against the Epstein-Barr Virus.

Exclusion Criteria

My liver is severely damaged or not functioning well.

I have not received a live vaccine in the last 4 weeks.

I haven't had a heart attack in the last 6 months and my heart condition is stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Desensitization Treatment

Highly sensitized patients are treated with belatacept and proteasome inhibitor to decrease calculated Panel of Reactive Antibodies (cPRA) and find a suitable kidney donor

1 month

Follow-up

Participants are monitored for safety and effectiveness after treatment, including episodes of Antibody Mediated Rejection (AMR) and Acute Cellular Rejection (ACR)

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Belatacept

Trial Overview The study tests if belatacept combined with a proteasome inhibitor can safely help find suitable donors for patients with high HLA sensitivity needing a kidney transplant. It aims to increase the chances of successful transplantation.

How Is the Trial Designed?

Group I: Patients treated with belatacept and proteasome inhibitor Experimental Treatment 1 Intervention

Highly sensitized patients will be treated with belatacept and proteasome inhibitor and monitored for decreasing calculated Panel of Reactive Antibodies (cPRA) and suitable kidney donor base don negative crossmatch

Belatacept is already approved in United States, European Union for the following indications:

Approved in United States as Nulojix for:

• Prophylaxis of organ rejection in adult patients receiving a kidney transplant

Approved in European Union as Nulojix for:

• Prophylaxis of organ rejection in adult patients receiving a kidney transplant

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

An accurate and precise assay for measuring belatacept serum concentrations was developed, showing a measurement range of 0.9-30 mg/L and high accuracy (91%-99%).

This assay was applied in a pharmacokinetic study involving 5 renal transplant recipients, allowing for the visualization of belatacept concentrations over time, which is crucial for optimizing immunosuppressive therapy post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients. Klaasen, RA., Egeland, EJ., Chan, J., et al.[2019]

Belatacept is an effective immunosuppressant for kidney transplant recipients, showing noninferior patient and allograft survival compared to cyclosporine in Phase 3 trials, with improved kidney function over three years.

While belatacept may offer benefits like better renal function and cardiometabolic health, it carries a risk of higher early rejection rates and potential increased risk of posttransplant lymphoproliferative disease, particularly in certain patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept in kidney transplantation. Wojciechowski, D., Vincenti, F.[2018]

Belatacept significantly improves renal function in kidney transplant recipients compared to traditional cyclosporine-based therapy, with a notable increase in estimated glomerular filtration rate (eGFR) of 13-15 mL/min at 1 year and 23-27 mL/min at 7 years, as shown in the BENEFIT study involving standard criteria donors.

In addition to enhancing kidney function, belatacept therapy is associated with lower rates of hypertension, high cholesterol, and new-onset diabetes compared to cyclosporine, although concerns about the risk of posttransplantation lymphoproliferative disorder and the cost of treatment may limit its widespread use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept for the prophylaxis of organ rejection in kidney transplant patients: an evidence-based review of its place in therapy. Hardinger, KL., Sunderland, D., Wiederrich, JA.[2020]

In a study of 219 kidney transplant patients, converting to belatacept led to a significant increase in kidney function, with the estimated glomerular filtration rate improving from 32 to 38 mL/min, indicating its efficacy in real-life settings.

Converting to belatacept within the first 3 months post-transplantation was identified as a key factor for better kidney function outcomes, although 8.2% of patients experienced acute rejection episodes, suggesting that while generally safe, monitoring is still necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conversion to Belatacept in Maintenance Kidney Transplant Patients: A Retrospective Multicenter European Study. Darres, A., Ulloa, C., Brakemeier, S., et al.[2022]

Belatacept is as effective as cyclosporine in preventing organ rejection in kidney transplant patients, with similar rates of patient and graft survival and acute rejection, while showing a significant advantage in reducing renal impairment after 12 months.

Patients treated with belatacept experienced fewer serious side effects, including lower rates of new-onset diabetes and better blood pressure and lipid levels compared to those on cyclosporine, indicating a potentially safer profile for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belatacept: in adult kidney transplant recipients. Garnock-Jones, KP.[2016]

Early conversion to belatacept-based immunosuppression after kidney transplantation significantly improved kidney function, as measured by eGFR, from 26.73 to 45.3 ml/min/1.73 m² within one year, while late conversion showed no significant change.

Both early and late conversion groups had a one-year allograft survival rate of 100%, but early conversion was associated with a higher rate of acute T-cell-mediated rejections, suggesting that the choice of immunosuppressants may influence rejection types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early conversion to belatacept-based immunosuppression regimen promotes improved long-term renal graft function in kidney transplant recipients. Moein, M., Dvorai, RH., Li, BW., et al.[2023]

Belatacept shows improved renal function and lower rates of new onset diabetes compared to traditional calcineurin inhibitors (CNI) in kidney transplant recipients, based on a meta-analysis of six randomized controlled trials.

There were no significant differences in acute rejection rates between belatacept and CNIs, suggesting that belatacept may reduce CNI-related toxicity without compromising transplant success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does belatacept improve outcomes for kidney transplant recipients? A systematic review. Talawila, N., Pengel, LH.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5724691/

Ten‐year outcomes in a randomized phase II study of kidney ... Death or graft loss status at 10 years posttransplant was assessed in 37.8% (28 of 74) of belatacept MI‐treated patients, 25.4% (18 of 71) of belatacept LI‐ ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1506027

Belatacept and Long-Term Outcomes in Kidney ... The reduction in the risk of death at 7 years was 38% with the more-intensive belatacept regimen and 45% with the less-intensive regimen as ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468024925001597

One-Year Outcomes After Belatacept Conversion in ... When looking at the eGFR evolution rate at the individual level, stable patients on belatacept showed significant improvement in graft function at 1 year and a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11108246/

Long-Term Outcomes after Conversion to a Belatacept ... After a mean follow-up time of 5.6 (2.6) years after conversion, 67 patients (28%) died in the belatacept group while 87 patients (36%) died in the CNI control ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522087159

Every 2-month belatacept maintenance therapy in kidney ... Belatacept results in improved kidney transplant outcomes, but utilization has been limited by logistical barriers related to monthly (q1m) intravenous ...

6. nulojixhcp.bmscustomerconnect.com nulojixhcp.bmscustomerconnect.com/pooled-safety.html

Selected Pooled Safety Data Polyoma virus-associated nephropathy can lead to deteriorating renal function and graft loss; consider reduction in immunosuppression, weighing risk to the ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3013525/

Five-Year Safety and Efficacy of Belatacept in Renal ... At the time of data cutoff, 76% of LTE belatacept and 62% of LTE CsA recipients remained in the study; all were ≥5 years after transplantation.